Mammalian cells have a higher concentration of potassium and a lower concentration of sodium than their extracellular environment. The mechanisms responsible for the unequal distribution of these ions are commonly ascribed to the presence of an energy requiring plasma membrane ATPase pump, and the presence of membrane channels that pass one ion selectively, while excluding others. This report deals with other mechanisms that might explain this heterogeneous distribution of ions. To study other mechanisms, we turned to a non-living system, specifically tendon/collagen to eliminate the contribution of the membrane pump and channels. A simple gravimetric method was designed to measure solute accumulation or exclusion during rehydration of a well-washed, carefully dried and well-characterized protein specimen (tendon/collagen). Exposure to physiological salt concentrations resulted in selective exclusion of Na+ over K+, whereas exposure to low-salt concentration resulted in accumulation of these solutes. It is postulated that this solute redistribution occurs in all hydrated proteins and is partially responsible for the heterogeneous solute distribution in cells presently assigned to pump and channel mechanisms. Physical and thermodynamic mechanisms are offered to explain the observed heterogeneous solute distributions.